Canadian Neighbor Pharmacy: The Role of Vasodilators in Patients with Progressive Systemic Sclerosis

Most studies investigating the role of systemic vasodilators in the treatment of pulmonary hypertension have concerned themselves with patients with primary pulmonary hypertension or cor pulmonale secondary to obstructive lung disease. A spectrum of responses, varying from an increase in cardiac output with a decrease in pulmonary artery pressures to simultaneous increases in pulmonary artery pressures and cardiac outputs, has been observed. Which patients will respond to vasodilators cannot be determined without invasive monitoring of systemic and pulmonary vascular pressures and cardiac outputs. Less commonly studied are those patients with secondary pulmonary hypertension from such entities as far-advanced interstitial lung disease (ILD) and progressive systemic sclerosis (PSS). Pulmonary hypertension occurs in from 35 to 80 percent of patients with PSS. The etiology of this hypertension is complex; in addition to hypoxia and loss of capillary units, there is probably some degree of reactive pulmonary vasoconstriction, the so-called Ravnauds phenomenon of the pulmonary vascular tree. Whether these patients will respond to vasodilators has not been studied in detail. This investigation determined the hemodynamic effect of various vasodilators in patients with for advanced ILD and PSS.

Group 1: Hydralazine treatment.—Three patients with severe sarcoidosis and one patient with mixed connective tissue disease.

Group 2: Nifedipine treatment.—Four patients with PSS.

After determining that the patients met our criteria for entry into the study, a balloon-tipped right heart catheter was inserted via a brachial or internal jugular vein into the right heart. The following baseline measurements were determined: systemic blood pressure (SBP), systolic and diastolic pulmonary artery pressures, PAP (mean), cardiac output (CO), systemic and pulmonary vascular resistance (SVR and PVR). The patients exercised on a bicycle ergometer at 75-100 watts for three to nine minutes, until they achieved a steady-state PAP. The website of Canadian Neighbor Pharmacy http://www.webmolecules.com/ is worked out in such a way to by simple and useful interface.

Following this baseline period, hydralazine (group 1) or nifedipine orally (group 2) was administered. The dose of drug was the amount which caused the resting SVR to fall by 20 to 40 percent from baseline (predrug) values. To attain this new SVR level usually required 25 to 50 mg of hydralazine or 20 to 50 mg of nifedipine. The above studies were repeated after 30 to 60 minutes. Analysis of variance was employed for intragroup comparisons. When a significant difference was found, a modified, paired t test was used (±SD).

After hydralazine administration there was no significant change in resting PAP, but there was a significant fall in resting SVR and an increase in CO (p

Group 2 (Table 2)

The four patients with PSS had moderate to severe restrictive lung disease (FVC 49 ±13 percent of predicted). Mean resting PAP prior to nifedipine administration was 22 ± 5.7 mm Hg. PAP increased with exercise to 39 ± 6.7 mm Hg. There was no other significant change in any other parameter from rest to exercise. Following nifedipine administration, there was no significant change in any resting parameter except SVR compared to predrug levels. With exercise, postdrug PAP increased to 39 ±9 mm Hg, which was not significantly different from baseline predrug exercise values. There was no other significant difference in any other parameter compared to predrug exercise levels.

Two patients had unusual hemodynamic reactions. One patient (who did not have pulmonary hypertension at rest or with exercise and therefore was not included in the study) had a dramatic increase in PAP (from 26/12 to 90/22 mm Hg) immediately following the injection of iced (0° F) saline solution for CO determinations. The PAP slowly returned to normal over ten minutes. During this time, the patient experienced systemic hypotension (BP 60/0 mm Hg), which

responded to IV fluid administration and leg raising.

During insertion of an arterial cannula, another patient complained of upper extremity pain (Raynauds phenomenon). The BP increased to 160/100 mm Hg, with a concomitant rise in the PWP from 8 to 32 mm Hg. PAP rose from 24/10 to 60/33 mm Hg. These changes reversed within ten minutes as the Raynauds phenomenon abated.

Discussion

Our results indicate that pulmonary hypertension at rest or with exercise is relatively common in patients with far-advanced ILD (group 1) and PSS (group 2). In group 1 treatment with hydralazine, an arterial vasodilator drug caused a minimal but nonsignificant decrease in exercising PAP, a significant decrease in resting SVR, and an increase in resting CO. Individual patients had some blunting of the exercise-induced pulmonary hypertension, although the biggest fall was 18 percent compared to predrug baseline exercise values.

In group 2 patients, although there was a significant decrease in resting SVR following nifedipine treatment, there was no decrease in PAP at rest or with exercise compared to predrug levels. In two patients who were followed up during long-term nifedipine therapy, there was no evidence for further improvement in these parameters.

TVvo patients with PSS had marked elevations in their PAP during our study; one patient had what could be interpreted as a Raynauds phenomenon of the pulmonary artery and the other had PAP elevations secondary to either transient left ventricular failure or a decrease in left ventricular compliance.

In conclusion: (1) the role for nifedipine in the therapy of patients with PSS remains unclear. Patients with a vasoconstrictive component to their pulmonary hypertension may be helped; (2) in selected patients with far-advanced ILD, hydralazine may blunt the exercise-induced pulmonary hypertension; and (3) elevation in PAP may be induced by invasive procedures or the injection of iced saline solution in patients with PSS.